Exposure to water tainted with toxic chemicals threatens human health. In excess of $100 billion will be required to eradicate the ~126,000 hazardous waste sites in the U.S. This effort incorporates innovative and cost-efficient technologies that are urgently needed for decontamination, environmental restoration and prompt protection of human health. Chlorinated solvents like tetrachloroethene (PCE) and trichloroethene (TCE), and their transformation products, dichloroethenes (DCEs) and vinyl chloride (VC), are major risk drivers and are linked to compromised immune systems, carcinogenesis, kidney and liver damage, and Parkinson's disease. Scientific understanding of the microbiology involved in reductive dechlorination to non-toxic ethene has invigorated cleanup efforts at chlorinated ethene sites. Although promising, detoxification and site closures are often not achieved when inefficient DCE and VC reductive dechlorination leads to DCE/VC stalls. Dehalococcoides mccartyi (Dhc) strains are keystone bacteria involved in the reductive dechlorination of DCEs and VC to environmentally benign ethene. Knowledge of Dhc ecophysiology and nutritional requirements promises to increase DCE and VC dechlorination rates, overcome DCE/VC stalls, and lead to more efficient bioremediation to reduce human contact with these dangerous chemicals. Detailed studies combining cultivation-based approaches, high-throughput sequencing, bioinformatics analyses, and state-of-the art analytical procedures will reveal the biogeochemical conditions, under which Dhc reductive dechloirnation activity is/is not constrained by adequate corrinoid cofactor supply. An innovative, high-throughput quantitative PCR tool (i.e., the B12-qChip) will be designed, validated and made available to the community to recognize when corrinoid bioavailability limits Dhc reductive dechlorination activity. Application of the new tool and knowledge will improve contaminated site management by enabling site specific treatment to achieve efficient detoxification, effectively protect human exposure to toxic and carcinogenic chemicals, reduce remediation times and costs, while mitigating negative secondary environmental impacts of bioremediation treatment (e.g., lower greenhouse gas emissions, stable pH avoids toxic metal release).